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Biochem Biophys Res Commun. 2008 Jul 18;372(1):30-4. doi: 10.1016/j.bbrc.2008.04.187. Epub 2008 May 14.

In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells.

Author information

1
Department of Microbial Pathogenesis & Immune Response, Meharry Medical College, 1005 D.B. Todd Jr. Boulevard, Nashville, TN 37208, USA.

Abstract

The regulation of vitamin D receptor (VDR), a key mediator in the vitamin D pathway, in breast cancer etiology has long been of interest. We have shown here that the transcriptional repressor protein SLUG inhibits the expression of VDR in human breast cancer cells. To explore the possibility that SLUG regulates the VDR gene promoter, we cloned a 628bp fragment (-613 to +15) of the human VDR gene promoter. This region contains three E2-box sequences (CAGGTG/CACCTG), the classical binding site of SLUG. SLUG specifically inhibited VDR gene promoter activity. Chromatin-immunoprecipitation (ChIP) assays revealed that SLUG is recruited on the native VDR gene promoter along with the co-repressor protein CtBP1 and the effector protein HDAC1. These data suggests that SLUG binds to the E2-box sequences of the VDR gene promoter and recruits CtBP1 and HDAC1, which results in the inhibition of VDR gene expression by chromatin remodeling.

PMID:
18485278
PMCID:
PMC2846599
DOI:
10.1016/j.bbrc.2008.04.187
[Indexed for MEDLINE]
Free PMC Article

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